| 2005 |
Wnt10b shifts mesenchymal precursor cell fate toward osteoblastogenesis and away from adipogenesis by inducing osteoblastogenic transcription factors Runx2, Dlx5, and osterix while suppressing adipogenic transcription factors C/EBPα and PPARγ; Wnt10b-/- mice have decreased trabecular bone confirming its endogenous role in bone formation. |
Transgenic mouse overexpression (FABP4-Wnt10b), Wnt10b knockout mice, pharmacological and genetic epistasis approaches, histomorphometry |
Proceedings of the National Academy of Sciences of the United States of America |
High |
15728361
|
| 2004 |
Wnt10b inhibits development of both white and brown adipose tissue in vivo; transgenic FABP4-Wnt10b mice show ~50% reduction in total body fat, resistance to diet-induced obesity, improved glucose tolerance and insulin sensitivity, and inability to maintain core body temperature (loss of brown adipose tissue function). |
Transgenic mouse model (FABP4-Wnt10b), histology, metabolic phenotyping, cold-exposure challenge |
The Journal of biological chemistry |
High |
15190075
|
| 2011 |
Wnt10b inhibits adipogenesis and stimulates osteoblastogenesis through a β-catenin-dependent mechanism; knockdown of β-catenin completely prevents both effects of Wnt10b on mesenchymal stem cell fate in bipotential ST2 cells and 3T3-L1 preadipocytes. |
Gain- and loss-of-function in ST2 and 3T3-L1 cells, β-catenin knockdown, osteoblastogenesis and adipogenesis assays |
Bone |
High |
21872687
|
| 2009 |
Intermittent parathyroid hormone (iPTH) increases Wnt10b production by bone marrow CD8+ T cells, which then activate canonical Wnt signaling in preosteoblasts to stimulate osteoblastic commitment, proliferation, differentiation, and lifespan; T-cell-null mice and mice lacking T-cell-produced Wnt10b show no anabolic response to iPTH. |
In vivo iPTH treatment, T-cell-null mice, conditional Wnt10b knockout in T cells, histomorphometry, Wnt signaling assays in preosteoblasts |
Cell metabolism |
High |
19723499
|
| 2018 |
Gut microbiota-derived butyrate induces expansion of intestinal and bone marrow regulatory T (Treg) cells; Treg cells promote assembly of a NFAT1-SMAD3 transcription complex in CD8+ T cells, driving expression of Wnt10b, which mediates bone anabolic effects; reconstitution with Wnt10b-/- CD8+ T cells prevents butyrate-induced bone formation. |
Probiotic/butyrate supplementation in mice, germ-free mice, Treg depletion, TCRβ-/- mice reconstituted with Wnt10b-/- CD8+ T cells, ChIP for NFAT1-SMAD3 complex, microCT |
Immunity |
High |
30446387
|
| 2013 |
WNT10B activates canonical β-catenin signaling in triple-negative breast cancer cells, leading to transcriptional upregulation of HMGA2 (demonstrated by ChIP); HMGA2 is necessary and sufficient for WNT10B-driven proliferation of TNBC cells; siRNA to HMGA2 decreases proliferation. |
ChIP analysis, siRNA knockdown, luciferase reporter assays, transgenic mouse tumor model, Western blotting |
EMBO molecular medicine |
High |
23307470
|
| 2018 |
In chemoresistant TNBC, WNT10B activates a β-CATENIN/HMGA2/EZH2 autoregulatory loop; HMGA2 and EZH2 displace Groucho/TLE1 from TCF-4 and serve as gatekeepers for K49 acetylation on β-CATENIN essential for transcription; HMGA2-EZH2 interacts with the PRC2 complex. |
Co-immunoprecipitation, MMTV-Wnt10b transgenic mice, Hmga2 haploinsufficiency, PDX model, Western blot, molecular epistasis |
Cancer research |
Medium |
30563890
|
| 2013 |
TGF-β1 stimulates Wnt10b production in osteoclasts through Smad2/3 activation (not AKT or MAPK); TGF-β1-induced osteoclast-derived Wnt10b promotes osteoblast mineralization; blocking Wnt10b with DKK1 suppresses this mineralization-promoting activity. |
In vitro osteoclast culture, TGF-β1 treatment, Smad2/3 signaling blockade, DKK1 inhibition, conditioned media osteoblast mineralization assay |
Endocrinology |
Medium |
23861379
|
| 2010 |
Wnt10b deficiency in null mice results in a progressive, age-dependent reduction in mesenchymal progenitor cells (assessed by colony-forming unit assays) and trabecular bone loss, with reduced expression of osteoblast differentiation markers in bone marrow stromal cells. |
Wnt10b-/- mice, microCT, histomorphometry, colony-forming unit assays, osteogenic gene expression analysis |
Journal of bone and mineral research |
High |
20499361
|
| 2005 |
Wnt10b deficiency in myoblasts increases adipogenic potential, contributing to excessive lipid accumulation in regenerating myofibers; overexpression of Wnt10b in aged myoblasts inhibits adipogenic gene expression and sustains myogenic differentiation; GSK-3 inhibition mimics Wnt10b overexpression effects. |
Wnt10b null myoblasts, Wnt10b overexpression, GSK-3 inhibition, adipogenic/myogenic differentiation assays, in vivo muscle regeneration analysis |
Molecular biology of the cell |
High |
15673614
|
| 1997 |
Overexpression of Wnt-10b in mammary glands of transgenic mice (MMTV-Wnt10b) causes hypermorphic ductal development, precocious alveolar formation in virgins, male gynecomastia bypassing androgen repression, and high susceptibility to mammary adenocarcinoma; co-expression with FGF-3/int-2 causes potent interaction and disorganized mammary epithelium. |
MMTV-Wnt10b transgenic mouse model, histology, tumor incidence analysis, MMTV-Wnt10b × MMTV-FGF3 cross |
Oncogene |
High |
9393971
|
| 2017 |
Wnt10b secreted from fibroblasts is transported via exosomes to breast cancer epithelial cells; paracrine Wnt10b from p85α-deficient fibroblasts promotes cancer progression through epithelial-to-mesenchymal transition via the canonical Wnt pathway. |
Conditioned media experiments, exosome isolation/characterization, co-culture, EMT marker analysis, Western blot |
Oncogene |
Medium |
28394344
|
| 2017 |
Fibroblast-derived exosomes (FD exosomes) mobilize Wnt10b toward lipid rafts, activating mTOR signaling via GSK3β and TSC2; autocrine Wnt10b-mTOR pathway is required for FD exosome-promoted axonal regeneration after optic nerve injury, as Wnt10b-deleted animals show strongly reduced regeneration. |
Wnt10b knockout mice, optic nerve injury model, lipid raft fractionation, mTOR signaling pathway analysis, in vitro neurite growth assays |
Cell reports |
Medium |
28683327
|
| 2012 |
miR-148a directly targets WNT10B mRNA via its 3'UTR (demonstrated by luciferase reporter assay); silencing of miR-148a in cancer-associated fibroblasts elevates WNT10B protein levels and promotes migration of endometrial cancer cell lines; re-introduction of miR-148a reduces WNT10B and impairs cancer cell migration. |
3'UTR luciferase reporter assay, miR-148a lentiviral overexpression, conditioned media migration assays, Western blot |
Oncogene |
High |
22890324
|
| 2003 |
In zebrafish, wnt10b and wnt1 provide partially redundant functions at the midbrain-hindbrain boundary (MHB); double deletion of both loci causes loss of pax2.1, en2, and her5 expression in the ventral MHB; wnt10b/wnt1 are required to maintain threshold levels of Pax2.1 and Fgf8 at the MHB. |
Zebrafish wnt1-wnt10b deficiency allele generation, morpholino knockdown, in situ hybridization, genetic epistasis with Pax2.1 and Fgf8 mutants |
Developmental biology |
High |
12591239
|
| 2020 |
Wnt10b is required for normal mitotic microtubule dynamics and chromosome segregation in human somatic cells; Wnt10b acts through a Wnt/STOP (LRP6-DVL-dependent, β-catenin-independent) pathway to suppress GSK3β activity; loss of Wnt10b causes increased microtubule growth rates in mitotic spindles, whole chromosome missegregation, and aneuploidy. |
Wnt10b knockdown/knockout in human somatic cells, live-cell imaging of mitosis, microtubule dynamics measurements, Wnt/STOP pathway analysis, chromosome segregation assays |
Life science alliance |
Medium |
33257473
|
| 2015 |
WNT10B causes nuclear transport and binding of both RAC1 and β-catenin in human corneal endothelial cells, activating Cyclin D1 expression and proliferation through simultaneously β-catenin-dependent and β-catenin-independent (RAC1) pathways. |
Nuclear fractionation, co-immunoprecipitation, reporter assays, proliferation assays in human corneal endothelial cells |
The Journal of biological chemistry |
Medium |
26370090
|
| 2014 |
The sclerostin-independent bone anabolic activity of iPTH is mediated exclusively by T-cell-produced Wnt10b; in T-cell-null mice and mice lacking T-cell Wnt10b expression, combined iPTH + anti-sclerostin antibody treatment is equivalent to anti-sclerostin antibody alone in increasing osteoblast pool and bone volume. |
T-cell-null mice, T-cell-specific Wnt10b knockout mice, anti-sclerostin antibody treatment, iPTH treatment, histomorphometry, microCT |
Journal of bone and mineral research |
High |
24357520
|
| 2019 |
NSD1 histone methyltransferase promotes Wnt10b expression by mediating H3K36me2 methylation at the Wnt10b locus; NSD1 knockout increases H3K27me3 and reduces H3K36me2, suppressing Wnt10b expression and inactivating the Wnt/β-catenin pathway in hepatocellular carcinoma cells. |
CRISPR/Cas9 NSD1 knockout, ChIP for histone marks at Wnt10b locus, Western blot, reporter assays, xenograft model |
Journal of experimental & clinical cancer research |
Medium |
31727171
|
| 2013 |
HIF-2α (but not HIF-1α) directly binds the Wnt10b enhancer region under hypoxic conditions to drive Wnt10b expression in adipogenic cells; hypoxia-conditioned medium containing Wnt10b activates canonical Wnt signaling (LRP6 phosphorylation, β-catenin-dependent transcription) and inhibits adipogenesis in normoxic cells. |
ChIP for HIF-2α at Wnt10b enhancer, HIF-2α-deficient cells, hypoxia-conditioned medium, Wnt reporter assays, LRP6 phosphorylation assay |
The Journal of biological chemistry |
Medium |
23900840
|
| 2016 |
XBP1s directly induces transcription of miR-148a by binding to a response element in the miR-148a promoter (demonstrated by point mutation analysis and ChIP); miR-148a binds the 3'UTR of Wnt10b mRNA to suppress Wnt10b expression and β-catenin activity during adipogenesis, constituting a post-transcriptional silencing axis XBP1s → miR-148a → Wnt10b. |
ChIP for XBP1s at miR-148a promoter, point mutation of XBP1 response element, 3'UTR reporter assay, miR-148a mimic/knockdown in 3T3-L1 cells |
Experimental & molecular medicine |
Medium |
27055562
|
| 2013 |
XBP1 transcription factor directly binds the Wnt10b promoter and suppresses Wnt10b expression, reducing β-catenin signaling and promoting adipogenic differentiation of 3T3-L1 preadipocytes; XBP1 and Wnt10b display reciprocal expression patterns during adipogenesis. |
XBP1 ChIP on Wnt10b promoter, reporter assays, siRNA knockdown, Western blot for β-catenin, 3T3-L1 adipogenesis assay |
FEBS letters |
Medium |
23603388
|
| 2017 |
MAT2A interacts with Ezh2 and MafK and is recruited to the Wnt10b promoter to repress Wnt10b expression by promoting H3K27 methylation; MAT2A-mediated suppression of Wnt10b inhibits Wnt/β-catenin signaling and promotes adipogenesis. |
Co-immunoprecipitation of MAT2A-Ezh2-MafK, ChIP for H3K27me3 and MAT2A at Wnt10b promoter, MAT2A overexpression/knockdown, adipogenesis assays |
Biochimica et biophysica acta. Molecular and cell biology of lipids |
Medium |
29133280
|
| 2019 |
Wnt10b is localized at the base of primary cilia in osteoblasts; sinusoidal electromagnetic fields (SEMFs) cause Wnt10b to disappear from/be released from primary cilia, activating Wnt/β-catenin signaling in osteoblasts; abrogation of primary cilia by IFT88 siRNA blocks SEMF-mediated Wnt10b/β-catenin activation and osteogenic differentiation. |
IFT88 siRNA knockdown, immunofluorescence localization of Wnt10b at primary cilia, Wnt10b siRNA, osteoblast differentiation assays in rat calvarial osteoblasts, in vivo microCT in rats |
Journal of bone and mineral research |
Medium |
30779853
|
| 2015 |
After myocardial infarction, Wnt10b is expressed in cardiomyocytes and localizes to intercalated discs; Wnt10b is transiently induced in peri-infarct cardiomyocytes; Wnt10b gain-of-function promotes cardiac repair by stimulating VEGFR2 expression in endothelial cells and angiopoietin-1 in vascular smooth muscle cells through NF-κB activation, coordinating neovascularization and reducing fibrosis. |
Histological localization in mouse and human hearts, coronary artery ligation/cryoinjury models, cardiomyocyte-specific Wnt10b gain-of-function mouse line, VEGFR2/Ang-1 expression analysis, NF-κB reporter assays |
Circulation research |
Medium |
26338900
|
| 2009 |
In skeletal muscle cells, Wnt10b and SREBP-1c show reciprocal expression; knockdown of SREBP-1 induces Wnt10b expression and activates Wnt/β-catenin pathway; silencing Wnt10b induces SREBP-1c expression; Wnt/β-catenin activation increases insulin sensitivity by decreasing intramyocellular lipid deposition through SREBP-1c downregulation and increasing glucose transport via differential Akt and AMPK activation. |
siRNA knockdown of SREBP-1 and Wnt10b, Wnt10b overexpression, GSK-3β inhibition, glucose transport assays, Akt/AMPK pathway analysis in myotubes |
PloS one |
Medium |
20041157
|
| 2022 |
BMI1 epigenetically represses Wnt10b transcription in spermatogonial stem cells (SSCs) by increasing H2AK119ub and decreasing H3K4me3 at the Wnt10b locus; BMI1 inhibition leads to Wnt10b upregulation, nuclear translocation of β-catenin, and impaired SSC maintenance; suppression of Wnt/β-catenin signaling restores SSC maintenance in BMI1-deficient SSCs. |
BMI1 knockout mouse model, chromatin modification analysis (H2AK119ub, H3K4me3), β-catenin localization, Wnt/β-catenin inhibition, SSC functional assays in vitro and in vivo |
International journal of biological sciences |
Medium |
35541907
|
| 2007 |
WNT10B activates β-catenin/Tcf signaling but also has β-catenin/Tcf-independent growth suppression activity; fibroblast growth factor (FGF) synergizes with WNT10B to switch it from growth suppressor to growth promoter; WNT10B is silenced by promoter DNA methylation in 46% of primary hepatocellular carcinomas. |
WNT10B overexpression in cancer cell lines, dominant-negative hTcf-4, mutant β-catenin transduction, anchorage-independent growth assay, 5-aza-2'deoxycytidine treatment, methylation analysis, FGF co-treatment |
Molecular biology of the cell |
Medium |
17761539
|
| 2007 |
WNT10B treatment of osteosarcoma cells (U2OS) activates Wnt, NF-κB, and Notch pathways; Wnt10b (but not Wnt3a) upregulates Notch-1, Jagged-1, and activates Notch-responsive genes Hes-1 and Hey-1, and stimulates NF-κB reporter activity; IL-1α and TNF-α are upregulated at transcript and protein levels. |
Wnt10b-expressing U2OS cell line, microarray analysis, NF-κB reporter assay, Hey-1 reporter assay, qRT-PCR, Western blot, comparison with Wnt3a |
Journal of cellular biochemistry |
Medium |
21321991
|
| 2006 |
WNT10B C256Y naturally-occurring missense variant abrogates the ability of WNT10B to activate canonical WNT signaling and block adipogenesis in functional assays, establishing loss of canonical signaling as the mechanism underlying this obesity-associated mutation. |
Functional assay of WNT10B C256Y mutant for canonical WNT signaling activation and adipogenesis inhibition, comparison to wild-type |
Diabetologia |
Medium |
16477437
|
| 2016 |
WNT10B mutations identified in oligodontia patients (p.Arg211Gln, p.Pro190Arg, p.Trp262*, p.Phe284Cys) cannot normally enhance canonical Wnt signaling in HEPG2 cells (TOPFlash reporter) and cannot efficiently induce endothelial differentiation of dental pulp stem cells. |
TOPFlash luciferase reporter assay, dental pulp stem cell endothelial differentiation assay, Sanger sequencing |
American journal of human genetics |
Medium |
27321946
|
| 2012 |
Wnt10b-induced hair follicle regeneration in vivo requires canonical Wnt signaling: Wnt10b causes nuclear translocation of β-catenin, and knockdown of β-catenin with siRNA abrogates Wnt10b-induced hair follicle telogen-to-anagen transition; siRNA knockdown of Wnt10b blocks anagen onset. |
Intradermal injection of adenovirus-Wnt10b in mice, β-catenin siRNA co-treatment, Wnt10b siRNA, immunofluorescence for nuclear β-catenin, hair follicle cycling assessment |
The Journal of investigative dermatology |
Medium |
22832493
|
| 2013 |
Ovariectomy expands short-term hematopoietic stem cells (ST-HSPCs) through CD40L expressed on T cells; CD40L is required for ovariectomy to stimulate T-cell Wnt10b production; Wnt10b activates Wnt signaling in HSPCs and stromal cells; ovariectomy fails to expand ST-HSPCs in CD40L-null mice and in mice lacking T-cell Wnt10b. |
Ovariectomy in CD40L-null mice, T-cell-specific Wnt10b null mice, bone marrow transplantation assays, HSPC flow cytometry |
Blood |
Medium |
23954891
|
| 2021 |
PTEN reduces BMP9-induced Wnt10b expression in mesenchymal stem cells through disrupting interaction between CREB and BMP/Smad1/5/9 signaling; p-CREB and p-Smad1/5/9 interact and are enriched at the Wnt10b promoter; PI3K inhibition (Ly294002) and rapamycin both reduce BMP9-induced Wnt10b expression, placing Wnt10b downstream of PI3K/mTOR and BMP/Smad signaling. |
Co-immunoprecipitation of CREB-Smad1/5/9, ChIP at Wnt10b promoter, PTEN overexpression/knockdown, PI3K and mTOR inhibitors, ALP activity and mineralization assays, in vivo bone mass assay |
Frontiers in cell and developmental biology |
Medium |
33614622
|
| 2011 |
Leucine-rich Amelogenin Peptide (LRAP) promotes osteogenesis and inhibits adipogenesis of MSCs by upregulating Wnt10b expression to activate canonical Wnt/β-catenin signaling; Wnt10b siRNA knockdown abrogates LRAP's effects on MSC fate. |
LRAP treatment of ST2 cells, Wnt10b siRNA knockdown, sFRP-1 Wnt inhibition, Wnt/β-catenin reporter assays, osteogenic/adipogenic differentiation assays |
Biomaterials |
Medium |
21663957
|
| 2006 |
Purified recombinant Wnt10b protein promotes differentiation of primary skin epithelial cells toward hair shaft and inner root sheath identity, inducing expression of keratin 1, keratin 2, loricrin, mHa5, mHb5, and reducing keratin 5; this differentiation involves the canonical Wnt signaling pathway (TCF reporter activation). |
Recombinant Wnt10b protein purification from lymphocyte supernatant, primary skin epithelial cell culture, immunocytochemistry, RT-PCR for differentiation markers, TCF reporter (pTOPFLASH) assay |
Biochemical and biophysical research communications |
Medium |
16510119
|
| 2012 |
FHL2 silencing reduces Wnt10b expression in mesenchymal cells, and Wnt10b overexpression overcomes the negative effect of FHL2 knockdown on osteoblast gene expression; FHL2 knockout mice show decreased Wnt5a and Wnt10b expression in bone marrow with reduced bone mass and osteoblast function. |
FHL2 shRNA knockdown, Wnt10b overexpression rescue, FHL2 knockout mice, histomorphometry, qRT-PCR of Wnt molecules and osteoblast genes |
Bone |
Medium |
23201222
|